The present invention relates generally to the design and use of medical devices, and more particularly to the design and use of implantable graft-port systems, devices and methods for establishing access to a fluid-filled internal body space of a patient including the patient's vascular system for blood treatments. In general, these blood treatments include, but are not limited to, hemodialysis, hemofiltration, hemodiafiltration, plasmapheresis, ultrafiltration, aquapheresis, n lipid pheresis and hemoperfusion. In the following description, the term “hemodialysis” (or “HD”) is generally used in connection with the present invention, but it is not intended to restrict the use of the device and methods of the present invention to hemodialysis. The subject invention may be used for other blood treatments, drug infusions, or any procedures that require access to a fluid-filled internal body space of a patient, for example. Lock solutions to prevent fowling and infection are also disclosed.
Access to a patient's vascular system can be established by a variety of temporary and permanent devices implanted under the patients skin. Temporary access can be provided by the direct percutaneous introduction of a needle through the patient's integument and into a blood vessel. While such a direct approach is relatively simple and suitable for some applications, such as intravenous feeding, intravenous drug delivery, and other applications which are limited in time, they are not suitable for hemodialysis, chemotherapy, and extracorporeal procedures that must be repeated periodically, sometimes for the duration of the patient's life. Hemodialysis and hemofiltration (also referred to as hemofiltration), both rely on separate draw and return catheters implanted in a vein and/or artery to allow extra corporeal treatment of the blood. Peritoneal dialysis, in contrast, relies on a single catheter implanted in the peritoneum to permit introduction and withdrawal of dialysate to permit in situ dialysis.
In 2012, the number of patients treated for end stage renal disease (ESRD) was estimated to be about 3 million. Of these patients, about 2.8 million were undergoing dialysis treatment. Medicare spends about $8 billion in dialysis procedures annually. Despite the significant costs, about 20% of dialysis patients in the United States die each year, most often from heart disease or infections. Dialysis treatment of individuals suffering from renal failure requires that blood be withdrawn and cycled through a dialysis machine that performs the function of the failed kidneys. Hemodialysis must be repeated at regular intervals and thus requires repeated punctures using dialysis needles. These relatively large gauge needles are required to promote the high flow rates required during dialysis. Frequent puncturing of autogenous arteriovenous access as well as prosthetic arteriovenous access with large bore needles can cause trauma, conduit degeneration, hematoma formation, pseudoaneurysm formation, loss of patency, or even hemorrhage and exsanguination.
Implanted Ports:
For hemodialysis and other extracorporeal treatment regimens, a variety of implantable ports have been proposed throughout recent decades. Typically, the port includes a chamber and an access region, such as a septum, where the chamber is attached to an implanted catheter which, in turn, is secured to a blood vessel. In the case of veins, the catheter is typically indwelling and in the case of arteries, the catheter may be attached by conventional anastomosis. These access methods permit only limited flow rates which can be problematic since they prolong the duration of the treatment (i.e. hemodialysis, hemofiltration, plasmaphoresis, apheresis). Moreover, limited flow rates may cause catheter blockages or plugging resulting from fibrin sheath or thrombosis formation over the distal end of the catheter.
Vasca and Biolink were familiar companies founded in the mid-1990s that lead the development of totally implantable HD ports based on the notion that prior implanted ports demonstrated low infection and thrombosis as compared to catheters used for chemotherapy applications. These companies surmised that the experiences learned from chemotherapy catheters could be replicated with HD ports. However, infection was an early problem, and thrombosis complications were only marginally better when compared with HD catheter infection rates. Unexpected problems occurred relating to large needle size, increased frequency of needle puncture and the necessary high blood flow rates, which imposed harsher conditions for hemodialysis access than those encountered during chemotherapy. Vasca and Biolink left the business by 2006 after considerable effort.
Vasca's port was named LifeSite® (FIG. 1). Vasca obtained U.S. approval for commercial distribution of LifeSite® and sold the product for approximately 5 years between about 2000 and 2005. LifeSite® was found to induce complications in patients, including surgical site infections and needle puncture site infections, which were aggravated by poor tissue healing around the needle puncture site. Use of the buttonhole (or “BH”) needle guidance technique in conjunction with LifeSite® was a factor in several infection episodes, in spite of various prophylactic measures (Ross, John J., et al., “Infections Associated with Use of the LifeSite® Hemodialysis Access System” Clinical Infectious Diseases 2002, 35:93-95). Misalignment of the buttonhole-type needle tract with the port's entrance resulted in failures to access correctly. Several factors may have contributed to poor performance, including:
(a) large needle size (i.e. 14 gauge) and poor closure of the needle tract after needle withdrawal;
(b) poor subcutaneous tissue healing and infection of the tissue around the needle tract;
(c) length of the needle tract in subcutaneous tissue, with the perpendicular, protruding needle exiting from patient's skin, susceptible to inadvertent bumping and/or tearing of tissue and dislodgement;
(d) the size and orientation of the implanted LifeSite® created high tensile stress in the tissue acting on the BH tract, which tended to open the BH tract;
(e) sealing/locking of the docked needle within the port was not reliable, and could be compromised by forces acting on the protruding needle, resulting in blood leakage during the HD treatment;
(f) in vivo shifting of the port relative to the BH tract caused misalignment of the port relative to the BH, so that needles were guided away from the port entrance, creating difficulty in accessing the blood and/or causing missed dialysis sessions;
(g) antimicrobial prophylaxis was not “locked” within the luminal passages of the port during the quiescent period, so microbes entering the catheter would not be exposed to a biocide; and
(h) the LifeSite® design was subject to “single fault” failure caused by needle dislodgement.
Biolink's port product was called Dialock® (FIG. 2). Dialock® was evaluated in a pilot clinical trial starting in 1996 and infections occurred quickly. It was realized that tissue infections from needle punctures could be reduced by injecting an antimicrobial “lock” solution into the tissue encapsulating the implanted port. However, serious tissue healing complications, caused by frequent puncturing with large needles, and the difficulty of establishing blood access remained a problem. These and other deficiencies in Dialock® performance would ultimately limit adoption of this port. Biolink Corporation declared bankruptcy around 2004.
One problem with the Dialock® device is that the entry ports are usually inclined at a substantial angle relative to the skin surface through which the access tube (i.e. needle or trocar) is introduced. Such angled access requires that the health care professional introducing the access tube guess the angle and estimate the optimum insertion point on the patient's skin. This uncertainty in the device penetration is perhaps why this type of design necessitates the use of an enlarged “funnel” for receiving and aligning the access tube as it is introduced. It would thus be advantageous to provide access ports having entry passages which are disposed generally “vertically” (i.e. at an angle which is substantially normal to the skin surface through which the access tube is being introduced). By penetrating the access tube “straight in”, it is much easier to align the access tube with the target opening. In this manner, the size of the orifice area can be reduced and the potential for skin damage can be minimized.
Implantable ports typically include a needle-penetrable septum which permits the percutaneous penetration of a needle or trocar into the internal chamber. The chamber, in turn, is connected to one end of the catheter, and the other end of the catheter is indwelling in the blood vessel. While workable, such designs suffer from a number of problems. Repeated penetration of the septum often leads to degradation over time, presenting a substantial risk of small particulates entering the blood stream. The implanted port may also require periodic replacement. Second, the passage of blood through the chamber or plenum will often encounter regions of turbulence or low flow, either of which can degrade the quality of blood over time and add to the time it takes to complete the patient's treatment regime.
Historically, attempts to solve these problems have included internal valve structures which isolate the interior of the port from the lumen of the implanted catheter when the port is not in use. Such valve-enabled ports, however, have their own shortcomings. For example, self-penetrating needles often cannot be used since they will be damaged by and/or cause damage to the port. In such instances, it is frequently necessary to use a catheter combined with a removable stylet, which is both more costly and more inconvenient than use of a simple needle. Moreover, many valved ports have no means or mechanism to assure that the valve is fully opened, particularly when insertion of the access needle opens the valve. Partial insertion of the needle can result in partial opening of the valve which can include a series of deleterious events.
A number of specific valve types have been incorporated into access port designs, including articulating valves such as leaflet valves, ball valves, and flapper valves. All such structures generally require that the access device be passed through the valve itself (i.e. the portion which closes the blood flow path through the valve) in order to cause the valve to open. Such a requirement presents the risk that the valve will be degraded by direct contact with the access device after repeated uses so that portions of the valve may be degraded and released into circulation. Such valves also represent significant risk of failure after repeated use or contact with a sharpened needle. Additionally, such valve structures can damage the access device as it is being introduced there through, thus potentially disrupting valve flow.
Many types of needle-actuated valved ports have been described over the years. Some ports include a duckbill valve which is opened by an elastomeric plug which is elongated by insertion of a needle. So long as the needle is fully inserted, the valve will be fully opened. It would be possible, however, to only partially insert the needle, resulting in only partial opening of the duckbill valve. Such partial opening could significantly degrade and alter the valve performance. Other needle-activated ports include locking mechanisms such as pinch clamps, displaceable balls and other elaborate features that increase the overall size of the port device. Large, bulky implanted ports can be obtrusive and uncomfortable for the patient when implanted. Furthermore, the geometry of some ports, particularly at the needle insertion point, may stretch the skin of the patient increasing the possibility of tearing and subsequent infection.
For these reasons, it would be desirable to provide improved valved implantable access ports for percutaneously accessing a patient's blood vessels, including both arteries and veins. The access ports will comprise a valve structure for isolating the port from an associated implanted catheter when the port is not in use. The valve will preferably provide little or no structure within the blood flow lumen of the access port and will even more preferably not require passage of an access tube, trocar or the like through the seating portion of a valve in order to open the valve. Furthermore, the port structure including the valve elements therein will have a substantially uniform cross-sectional area and will present no significant constrictions or enlargements to disturb or impede fluid flow there through. The port designs will permit percutaneous access using a conventional needle (i.e., fistula needle or standard trocar) or a proprietary needle without damaging the port or the needle. Still more preferably, the ports will include means for keeping the valve structures open in response to insertion of the needle or other access device without the needle becoming dislodged before the treatment is concluded. It would also be advantageous to provide increased flow rates without increasing the diameter of the catheter to reduce treatment time and thus improve the quality of life for the patient. Ports and valves according to the present invention will meet at least some of these objectives.
Information related to attempts to address these problems can be found in U.S. Pat. Nos. 3,998,222; 4,108,173; 4,181,132; 4,496,343; 4,534,759; 4,569,675; 4,778,452; 4,983,162; 5,053,013; 5,057,084; 5,120,313; 5,180,365; 5,226,879; 5,281,199; 5,263,930; 5,350,360; 5,417,656; 5,421,814; 5,476,451; 5,503,630; 5,520,643; 5,527,277; 5,527,278; 5,562,617; 5,637,088; 5,702,363; 5,704,915; 5,741,228; 5,755,780; 5,954,691; 5,989,239; 6,007,516; 6,022,335; 6,261,257; 6,582,409; 7,056,316; 7,131,192; 7,473,240; 7,803,143; 7,806,122; 8,151,801; 8,348,909 and U.S. Patent Application Publication Numbers 2007/0265584; 2011/0264104; 2014/0018721; 2014/0024998; 2014/0128792 as well as European Patent Application Numbers: EP 1550479; EP 2686033; EP 2300071 and International Patent Application Numbers: WO 95/19200; WO 96/31246; WO 97/047338; WO 98/35710; WO 99/38438; WO 07/061787; WO 09/152488; WO 10/015001; and WO 12/125927, for example.
Lock Solutions:
The need to leave catheters implanted for a prolonged period raises a number of concerns. First, the catheters can become infected requiring treatment of the patient and often requires removal of the catheter. This is a particular problem with transcutaneous catheters where the skin penetration is a common route of infection. Urinary catheterization exposes patients to increased risk of urinary, kidney and blood (sepsis) infections. Some other catheter-related infectious complications include septic shock, endocarditis, septic arthritis, osteomyelitis and epidural abscess. Biofilms of infectious bacteria and yeasts often colonize indwelling catheters. Second, implanted catheters can often become plugged or fouled over time. Catheter malfunction is often due to extrinsic and/or intrinsic thrombosis, and has been found to be the most common indication for catheter removal. This is a particular problem with intravascular catheters where clotting and intrinsic thrombus formation (i.e. within the catheter lumen) can be problematic. Extrinsic thrombosis, including central venous thrombosis, is also an important and common complication.
To reduce problems associated with thrombus formation, it is now common to “lock” intravascular access catheters between successive uses. Locking typically involves first flushing the catheter with saline to remove blood, medications, cellular debris and other substances from the catheter lumen. After the catheter has been flushed, a locking solution, typically heparin, is then injected to displace the saline and fill the lumen. The heparin locking solution both excludes blood from the lumen and actively inhibits clotting and thrombus formation within the lumen. To address infection, various antimicrobial substances have been combined with the locking solution in order to inhibit infection at the same time that thrombosis is being inhibited. However, problems with current and continuously emerging resistance to antimicrobial substances, as well as the over-use (and hence the increased risk of developing resistance) of anti-microbials, is an ever-growing concern.
While generally effective, the use of heparin locks suffers from a number of problems and disadvantages. For example, some thrombi may still form at the distal tip of the catheter despite the use of heparin. The need to prepare a heparin solution at the end of every catheter treatment session is time-consuming and presents an opportunity for error by a caregiver. Additionally, heparin has been shown to stimulate biofilm formation which makes it necessary to combine an antimicrobial compound in the heparin lock solution. Heparin is also associated with potentially adverse effects, including heparin-induced thrombocytopenia and bleeding risks.
Various acids have been proposed for use as antimicrobial catheter lock solutions. However, high concentrations of these acids have been shown to cause hemolysis of red blood cells and other harmful effects. Citrate, an ionic form of citric acid, will chelate the divalent cations including the calcium ions in blood and tissue. Serious symptoms have been reported when the ionized calcium blood level decreases. Spillage of extra locking solution into the patient includes miscalculating the lock volume, multiple instillations of solution into the same lumen and even deliberate over injection of solution to clear an occluded catheter. Thus, there is legitimate concern that risks of using concentrated sodium citrate for a catheter lock are not well understood.
Therefore, it would also be desirable to provide improved catheter lock solutions and locking methods to inhibit fouling of the catheter lumen and/or reduce the chance of infection, preferably both. In particular, such methods should be cidal against a broad spectrum of microorganisms and discourage the development of resistant microbes without damaging blood and/or tissue cells. The lock should be relatively inexpensive, non-toxic, easy to store, compatible with the catheter and port materials, safe if inadvertently infused systemically, easy to implement, require minimum or no preparation, and be useful with most or all types of implanted catheters, including hemodialysis and hemofiltration catheters, IV catheters, peritoneal dialysis catheters, urinary catheters, chemotherapy catheters, and the like. At least some of these objectives will be met by the invention described hereinafter.
Information related to attempts to address these problems can be found in U.S. Pat. Nos. 4,114,325; 4,929,242; 5,077,281; 6,635,243; 6,423,706; 6,679,870; 6,685,694; 6,824,532; 6,958,049 and U.S. Patent Application Publication Numbers: 2003/0175323; 2005/0037048; 2005/0043673; 2005/0181008; 2006/0024360; 2006/0052757; 2006/0062850; 2006/0094690; 2006/0177477; 2006/0253063; 2006/0257390; 2007/0292355; 2008/0118544; 2010/0249747 and 2011/0311602 as well as International Patent Application Number: WO 2000/01391, for example. Citrate has been discussed as a locking solution in various concentrations or in combination with other compounds in numerous publications including, for example, Ash et al., ASAIO Journal, (2000) 46(2):222; Mandolfo et al., Journal of Vascular Access, (2006) 7(3):99-102; Dogra et al., Journal of the American Society of Nephrology, (2002) 13(8):2133-2139; and Meeus et al., Blood Purification (2005) 23(2):101-105.
Various graft-port devices, methods for establishing access to a vascular system, and lock solutions, including some embodiments of the invention, can mitigate or reduce the effect of, or even take advantage of, some or all of these potential problems.
For the foregoing reasons, there is a legitimate need for effective and efficient ways to provide subcutaneously-implantable graft-port systems, devices and methods for establishing access to a vascular system of a patient that requires periodic ongoing extracorporeal blood treatment.
It would be desirable to leverage the advantages of a graft access while maintaining an easy-to-use port interface in order to decrease miscannulation and promote intra-session hemostasis. It would be particularly beneficial to also provide a graft-port systems, devices and methods for establishing vascular access to a patient to facilitate some or all of the following: 1) reduce the overall size of the implanted port; 2) simplify the locking mechanism to reduce the form factor of the port; 3) reduce the risk of foreign contaminants from invading the port; 4) decrease the incidence of bacteremia and sepsis; 5) simplify the surgical implantation and use of the device for health care professionals; 6) reduce the cross-sectional needle sealing area; 7) enhance overall safety via secure connections; 8) increase the quality of life and reduce treatment pain for the patient; 9) increase blood flow through the device during use; and 10) provide a lock solution to prevent fowling and infection. These attributes would increase treatment efficiency and improve the longevity and quality of life for the patient.